Devices made from porous materials for the controlled and continuous delivery of an active agent are known to the prior art. Generally, the agent is embedded in the material and its release therefrom often is adversely influenced by internal and external conditions. For example, U.S. Pat. No. 2,478,182 issued to Consolazio discloses a tablet comprising compressed granules of a common salt that pass through a No. 40 U.S. standard sieve, about 420 micron size. The tablet has an internally disposed cellular stroma of a thin, permeable dialyzing film. The film is made of cellulose acetate or cellulose nitrate. The cells of the stroma contain the salt so that, in dissolution, fluid dialyzes into the cellular compartment and the material dialyze out. The Consolazio patent also discloses that when the cellular compartments become engorged with fluid, the compartment burst and the desired substance is liberated therefrom to the exterior of the tablet. This mechanism for the salt results in a solution time of about 60 to 80 minutes for a ten grain tablet. The salt is released in this short time because the tablets of Consolazio are basically all salt with a little polymer binder. The tablet of Consolazio example contains 0.65 grain of salt and about 4 mg of polymer, and it has a salt to polymer ratio of 9 to 1, and for a 10 grain salt tablet, a salt to polymer ratio of about 16 to 1. The large size of Consolazio's salt granules coupled with these kinds of ratios lead to release by bulk-flow and quick spill-out to the surrounding fluid. These features preclude the use of the tablets as controlled, prolonged, diffusional agent delivery devices.
The prior art also includes U.S. Pat. No. 2,846,057 issued to patentee Polin. This patent discloses a device consisting of a porous cellophane wall surrounding sodium fluoride, that is released by water flowing into the pores to dissolve and leach it from the device. Controlled release is hard to obtain with this device because release is governed by external conditions and not by the device. That is, the amount of fluoride released changes with the rate of flow of water, with higher rates increasing the amount released, and lower rates decreasing the amount released over time. The patent does not teach a multi-structured system having a given surface area for controlled release over time. Another device is disclosed in United States Pat. No. 2,928,770 issued to Bardani. The device of the Bardani patent consists in a plurality of medicament layers separated by membranes having pores containing a pore closure substance. The pore closure substance is represented by a softened wax that is disclosed as being removable in the gastrointestinal tract by intestinal fluid. This device cannot be relied upon for controlled release as it requires in situ removal of the pore closure substance which is both difficult to achieve and is dominated by unregulated external conditions and not by the device per se.
In prior art U.S. Pat. No. 3,146,169 issued to Stephenson and Spence, there is disclosed a tablet formulation comprising a solid, inner medicated portion dissolvable in the fluid of the gastrointestinal tract. The portion is surrounded by an outer non-medicated portion which impermeable to medicament and fluids, insoluble, indigestible and unabsorbable in the fluid of the gastrointestinal tract. It appears the medicated portion is released by convection and diffusion. Delivery by convection will occur due to turbulence set up in the environment at the aperture of the tablet. This turbulence can exhibit a change in velocity that varies erratically in magnitude and direction, and as such the tablet does not lend itself for classification as a controlled, prolonged drug delivery device.
Similarly, in U.S. Pat. No. 3,538,214, Polli, Shoop and Grim disclose a device consisting of drug coated with a film of waterinsoluble plastic containing a modifying agent that is soluble at a certain pH. When this device is in the gastrointestinal tract, the modifying agent is partially or fully dissolved from the film by gastrointestinal fluid to form a porous film. This lets fluid through the film to dissolve the drug and leach it outwards through the pores into the tract. Controlled release is difficult to achieve with this device, because the selection of the modifying agent is based on the unknown acid and alkaline states of the gastrointestinal tract, which concomitantly influences pore formation and the exposure of drug to fluid. In U.S. Pat. No. 3,977,404, patentee Theeuwes discloses an osmotic device having a semipermeable wall and a microporous reservoir containing an agent that exhibits an osmotic pressure gradient across the semipermeable wall against an external fluid. The device releases agent by imbibing fluid through the semipermeable wall into the device, generating a hydrostatic pressure in the device that pumps agent from the device. The device operates by osmotic principles, and it cannot be converted to a diffusional device.
Another device designed for the release of drug from an inert plastic matrix is described by Sjorgen in Acta Pharm. Suecia, Volume 8, pages 153 to 158, 1971, and by D. Arcy, et at., in J. Pharm. Sci., Volume 60, pages 1028 to 1033, 1971. The device disclosed in these references consists of a porous poly(vinyl chloride) matrix having drug contained therein. Several disadvantages are associated with this device that tend to diminish its use as a reliable and dependable device. For example, the rate of release declines over time because the device lacks a means for governing the diffusional surface area exposed to a fluid environment of use. The unrestricted surface subjects the entire device to slight changes in the direction and velocity of fluid, which alters the amount and the rate of drug released by the device. Another disadvantage is the diffusional paths are not controlled in any direction, and as they increase and interact in all directions, the rate of release becomes unpredictable. Both of the above events cause the rate of release from the matrix to decrease as a function of time. These uncertainties restrict the application of the device, and present the rate of release from being known during its use. A similar device is set forth by Levesque in U.S. Pat. No. 2,987,445.